Molecular Profile |
Indication/Tumor Type |
Response Type |
Therapy Name |
Approval Status |
Evidence Type |
Efficacy Evidence |
References |
FLT3 exon16
|
acute myeloid leukemia
|
sensitive
|
Cytarabine + Daunorubicin + Midostaurin
|
Guideline |
Actionable |
Rydapt (midostaurin), in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine), is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).
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detail...
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FLT3 exon16
|
acute myeloid leukemia
|
sensitive
|
Cytarabine + Daunorubicin + Midostaurin
|
Guideline |
Actionable |
Rydapt (midostaurin), in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine), is included in guidelines as first-line treatment for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (PMID: 32171751; ESMO.org).
|
32171751
detail...
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FLT3 exon16
|
acute myeloid leukemia
|
sensitive
|
Gilteritinib
|
Guideline |
Actionable |
Xospata (gilteritinib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).
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detail...
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FLT3 exon16
|
acute myeloid leukemia
|
sensitive
|
Gilteritinib
|
Guideline |
Actionable |
Xospata (gilteritinib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (PMID: 32171751; ESMO.org).
|
32171751
detail...
|
FLT3 mutant
|
acute myeloid leukemia
|
sensitive
|
Cytarabine + Venetoclax
|
Guideline |
Actionable |
Venclexta (venetoclax) in combination with Cytosar-U (cytarabine) is included in guidelines for adult patients with acute myeloid leukemia harboring a FLT3 mutation (NCCN.org).
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detail...
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FLT3 mutant
|
acute myeloid leukemia
|
sensitive
|
Cytarabine + Venetoclax
|
Phase Ib/II |
Actionable |
In a Phase I/II trial, Venclexta (venetoclax) in combination with low-dose cytarabine resulted in complete remission or complete remission with incomplete count recovery in 44% (7/16) of patients with acute myeloid leukemia harboring FLT3 mutations who were ineligible for intensive chemotherapy (ASH Annual Meeting, Dec 2018, Abstract 284; NCT02287233).
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detail...
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FLT3 mutant
|
acute myeloid leukemia
|
sensitive
|
Cytarabine + Daunorubicin + Midostaurin
|
FDA approved - Has Companion Diagnostic |
Actionable |
In a Phase III trial that supported FDA approval, treatment with Rydapt (midostaurin), combined with Cytosar-U (cytarabine) and Daunorubicin, improved overall survival (HR=0.78, p=0.009) and event-free survival (HR=0.78, p=0.002) in patients with FLT3-mutant (ITD, D835X, and I836X mutations) acute myeloid leukemia compared to Cytosar-U (cytarabine) and Daunorubicin with placebo (PMID: 28644114; NCT00651261).
|
28644114
detail...
detail...
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FLT3 mutant
|
acute myeloid leukemia
|
sensitive
|
Cytarabine + Daunorubicin + Midostaurin
|
Phase Ib/II |
Actionable |
In a Phase Ib clinical trial, Rydapt (midostaurin) treatment after Daunorubicin and Cytosar-U (cytarabine) induction resulted in complete remission in 92% (12/13) of acute myeloid leukemia patients carrying FLT3 mutations, although overall survival rate was similar to patients with wild-type FLT3 (PMID: 22627678).
|
22627678
|
FLT3 mutant
|
acute myeloid leukemia
|
sensitive
|
Crenolanib
|
Phase I |
Actionable |
In a Phase I trial, Crenolanib treatment resulted in complete response (CR) in 39% (7/18), partial response (PR) in 11% (2/18), and an overall survival (OS) of 234 days in AML patients harboring FLT3 mutations (D835X, ITD, or both) that received no prior therapy, and CR in 17% (6/36), PR in 14% (5/36), and OS of 94 days in those progressed on TKIs (J Clin Oncol 34, 2016 (suppl; abstr 7008)).
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detail...
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FLT3 mutant
|
acute myeloid leukemia
|
sensitive
|
Azacitidine + Venetoclax
|
Guideline |
Actionable |
Venclexta (venetoclax) in combination with Vidaza (azacitidine) is included in guidelines for adult patients with acute myeloid leukemia harboring a FLT3 mutation (NCCN.org).
|
detail...
|
FLT3 mutant
|
acute myeloid leukemia
|
sensitive
|
Decitabine + Venetoclax
|
Guideline |
Actionable |
Venclexta (venetoclax) in combination with Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring a FLT3 mutation (NCCN.org).
|
detail...
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FLT3 mutant
|
acute myeloid leukemia
|
sensitive
|
UNC2025
|
Preclinical |
Actionable |
In a preclinical study, UNC2025 inhibited FLT3 activation and growth of acute myeloid leukemia cells harboring a FLT3-ITD mutation in culture (PMID: 25068800).
|
25068800
|
FLT3 mutant
|
acute myeloid leukemia
|
sensitive
|
Gilteritinib
|
Phase Ib/II |
Actionable |
In a Phase I/II trial, treatment with Gilteritinib (ASP2215) resulted in an overall response rate of 49% (93/191) in patients with relapsed or refractory acute myeloid leukemia harboring FLT3 mutations, compared to 12% (7/58) in patients with wild-type FLT3 (PMID: 28645776; NCT02014558).
|
detail...
28645776
|
FLT3 mutant
|
acute myeloid leukemia
|
sensitive
|
Gilteritinib
|
FDA approved - Has Companion Diagnostic |
Actionable |
In a Phase III trial (ADMIRAL) that supported FDA approval, Xospata (gilteritinib) treatment resulted in complete remission (CR) or CR with partial hematologic recovery in 21% (29/138) of patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD), D835, or I836 mutation (FDA.gov; NCT02421939).
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detail...
detail...
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FLT3 mutant
|
acute myeloid leukemia
|
sensitive
|
Selinexor + Sorafenib
|
Phase Ib/II |
Actionable |
In a Phase I/II trial, combination of Selinexor and Nexavar (sorafenib) treatment resulted in complete remission in 29% (4/14) and more than 50% blast reduction in 14% (2/14) of patients with acute myeloid leukemia harboring FLT3 ITD and/or D835 mutations (ASH, 59th Annual Meeting and Exposition, Dec 2017, Abstract 1344; NCT01607892).
|
detail...
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FLT3 mutant
|
acute myeloid leukemia
|
sensitive
|
E6201
|
Preclinical |
Actionable |
In a preclinical study, acute myeloid leukemia cell lines harboring FLT3 mutations demonstrated increased sensitivity to E6201 induced growth inhibition and apoptosis in culture compared to FLT3 wild-type cells (PMID: 26822154).
|
26822154
|
FLT3 mutant
|
acute myeloid leukemia
|
sensitive
|
Azacitidine + Midostaurin
|
Phase Ib/II |
Actionable |
In a Phase Ib/II trial, acute myeloid leukemia patients harboring a FLT3 mutation demonstrated an improved remission duration when treated with the combination therapy, Rydapt (midostaurin) and Vidaza (azacitidine) (PMID: 25530214).
|
25530214
|
FLT3 mutant
|
acute myeloid leukemia
|
sensitive
|
Zotiraciclib
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, Zotiraciclib (TG02) inhibited growth of FLT3-mutated acute myeloid leukemia cells in culture, resulted in complete tumor regression in cell line xenograft animal models (PMID: 21860433).
|
21860433
|
FLT3 act mut
|
acute myeloid leukemia
|
sensitive
|
VS-5584
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, VS-5584 inhibited PI3K/mTOR signaling and cell proliferation in a FLT3-ITD positive human acute myeloid leukemia cell line in culture, and inhibited tumor growth in xenograft models (PMID: 23270925).
|
23270925
|
FLT3 act mut
|
acute myeloid leukemia
|
sensitive
|
Palbociclib
|
Preclinical |
Actionable |
In a preclinical study, Ibrance (palbociclib) blocked growth, induced apoptosis, and inhibited STAT activation in human FLT3-ITD positive human acute myeloid leukemia cells in culture (PMID: 27099147).
|
27099147
|
FLT3 act mut
|
acute myeloid leukemia
|
sensitive
|
TCS 359
|
Preclinical |
Actionable |
In a preclinical study, TCS-359 inhibited growth of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147).
|
27099147
|
FLT3 act mut
|
acute myeloid leukemia
|
sensitive
|
Crenolanib
|
Phase II |
Actionable |
In a Phase II trial, relapsed or refractory acute myeloid leukemia patients harboring FLT3 activating mutations without a history of FLT3 therapy demonstrated a significantly greater overall survival and event free survival compared to those that had prior FLT3 therapy when treated with Crenolanib (ASH meeting, Dec 2014, abstract #389).
|
detail...
|
FLT3 act mut
|
leukemia
|
sensitive
|
Pexidartinib
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, PLX3397 inhibited FLT3 autophosphorylation in leukemia cells overexpressing FLT3 or harboring FLT3 activating mutations, and inhibited growth of leukemia cells harboring FLT3-ITD mutations in culture and in cell line xenograft models (ASH Annual Meeting Abstracts 2011 118: 3632).
|
detail...
|
FLT3 act mut
|
acute myeloid leukemia
|
sensitive
|
Palbociclib + TCS 359
|
Preclinical |
Actionable |
In a preclinical study, Ibrance (palbociclib) following TCS-359 treatment enhanced growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147).
|
27099147
|
FLT3 act mut
|
acute myeloid leukemia
|
sensitive
|
Palbociclib + Quizartinib
|
Preclinical |
Actionable |
In a preclinical study, Ibrance (palbociclib) and Quizartinib (AC220) were synergistic towards growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147).
|
27099147
|
FLT3 act mut
|
acute myeloid leukemia
|
sensitive
|
Palbociclib + SGI-1776
|
Preclinical |
Actionable |
In a preclinical study, Ibrance (palbociclib) and SGI-1776 were synergistic towards growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147).
|
27099147
|
FLT3 act mut
|
acute myeloid leukemia
|
sensitive
|
Palbociclib + Tandutinib
|
Preclinical |
Actionable |
In a preclinical study, Ibrance (palbociclib) and tandutinib (MLN518) were synergistic towards growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147).
|
27099147
|
FLT3 act mut
|
acute myeloid leukemia
|
sensitive
|
Cytarabine + Daunorubicin + Sunitinib
|
Phase Ib/II |
Actionable |
In a Phase Ib/II trial, 59% (13/22) of acute myeloid leukemia patients harboring FLT3 activating mutations achieved complete remission following treatment with Sutent (sunitinib) in combination with Cytarabine and Daunorubicin (PMID: 25818407).
|
25818407
|